Predicting flows through microfluidic circuits with fluid walls

The aqueous phase in traditional microfluidics is usually confined by solid walls; flows through such systems are often predicted accurately. As solid walls limit access, open systems are being developed in which the aqueous phase is partly bounded by fluid walls (interfaces with air or immiscible liquids). Such fluid walls morph during flow due to pressure gradients, so predicting flow fields remains challenging. We recently developed a version of open microfluidics suitable for live-cell biology in which the aqueous phase is confined by an interface with an immiscible and bioinert fluorocarbon (FC40). Here, we find that common medium additives (fetal bovine serum, serum replacement) induce elastic no-slip boundaries at this interface and develop a semi-analytical model to predict flow fields. We experimentally validate the model’s accuracy for single conduits and fractal vascular trees and demonstrate how flow fields and shear stresses can be controlled to suit individual applications in cell biology.

Deep Multi-Segmentation Approach for the Joint Classification and Segmentation of the Retinal Arterial and Venous Trees in Color Fundus Images

The analysis of the retinal vasculature represents a crucial stage in the diagnosis of several diseases. An exhaustive analysis involves segmenting the retinal vessels and classifying them into veins and arteries. In this work, we present an accurate approach, based on deep neural networks, for the joint segmentation and classification of the retinal veins and arteries from color fundus images. The presented approach decomposes this joint task into three related subtasks: the segmentation of arteries, veins and the whole vascular tree. The experiments performed show that our method achieves competitive results in the discrimination of arteries and veins, while clearly enhancing the segmentation of the different structures. Moreover, unlike other approaches, our method allows for the straightforward detection of vessel crossings, and preserves the continuity of the arterial and venous vascular trees at these locations.

Development of Novel Fractal Method for Characterizing the Distribution of Blood Flow in Multi-Scale Vascular Tree

Blood perfusion is an important index for the function of the cardiovascular system and it can be indicated by the blood flow distribution in the vascular tree. As the blood flow in a vascular tree varies in a large range of scales and fractal analysis owns the ability to describe multi-scale properties, it is reasonable to apply fractal analysis to depict the blood flow distribution. The objective of this study is to establish fractal methods for analyzing the blood flow distribution which can be applied to real vascular trees. For this purpose, the modified methods in fractal geometry were applied and a special strategy was raised to make sure that these methods are applicable to an arbitrary vascular tree. The validation of the proposed methods on real arterial trees verified the ability of the produced parameters (fractal dimension and multifractal spectrum) in distinguishing the blood flow distribution under different physiological states. Furthermore, the physiological significance of the fractal parameters was investigated in two situations. For the first situation, the vascular tree was set as a perfect binary tree and the blood flow distribution was adjusted by the split ratio. As the split ratio of the vascular tree decreases, the fractal dimension decreases and the multifractal spectrum expands. The results indicate that both fractal parameters can quantify the degree of blood flow heterogeneity. While for the second situation, artificial vascular trees with different structures were constructed and the hemodynamics in these vascular trees was simulated. The results suggest that both the vascular structure and the blood flow distribution affect the fractal parameters for blood flow. The fractal dimension declares the integrated information about the heterogeneity of vascular structure and blood flow distribution. In contrast, the multifractal spectrum identifies the heterogeneity features in blood flow distribution or vascular structure by its width and height. The results verified that the proposed methods are capable of depicting the multi-scale features of the blood flow distribution in the vascular tree and further are potential for investigating vascular physiology.

Towards blood flow in the virtual human: efficient self-coupling of HemeLB

Many scientific and medical researchers are working towards the creation of a virtual human—a personalized digital copy of an individual—that will assist in a patient’s diagnosis, treatment and recovery. The complex nature of living systems means that the development of this remains a major challenge. We describe progress in enabling the HemeLB lattice Boltzmann code to simulate 3D macroscopic blood flow on a full human scale. Significant developments in memory management and load balancing allow near linear scaling performance of the code on hundreds of thousands of computer cores. Integral to the construction of a virtual human, we also outline the implementation of a self-coupling strategy for HemeLB. This allows simultaneous simulation of arterial and venous vascular trees based on human-specific geometries.

Abstract 17136: Pulmonary Arterial and Venous Fractal Dimension as a Marker of Pulmonary Arterial Hypertension

Introduction: PAH is characterized by a loss of pulmonary vascular complexity. In this study, total, arterial, and venous vasculatures of patients with PAH and with ePAH were analyzed using fractal analysis and compared against controls Methods: Data from 1514 consecutive right heart catheterizations from 4/27/2011 to 10/2/2018 representing subjects referred to our dyspnea center were searched for availability of imaging. 388 CT angiography (CTA) scans were identified (used given retrospective availability of thin slice reconstructions). Three initial cohorts (no overlap) were identified from individuals in this set. Control patients had normal resting and exercise hemodynamics and no history of cardiopulmonary disease. The second group met the current definition of PAH (resting mean pulmonary arterial pressure >20mmHg, pulmonary vascular resistance >3 Wood Units, pulmonary capillary wedge pressure <15mmHg). The third group (ePAH) had normal resting hemodynamics but age adjusted evidence of PAH with exercise. Pulmonary vascular trees were reconstructed; total, arterial, and venous trees were separated; and fractal dimensions were measured using a 3D box counting method for each tree. Comparisons were made using the Wilcoxon Rank Sum test (R 3.5). Results: Venous fractal dimensions of controls (2.10±0.07) were higher than those of PAH (2.03±0.08; p=3e-6) and of ePAH (2.04±0.13; p=0.008). Total fractal dimension also yielded higher values for controls (2.30±0.05) compared against PAH (2.28±0.07; p=0.009) and ePAH (2.26±0.10; p=0.04). No significant differences were found between arterial fractal dimensions of controls (2.17±0.04) against those of PAH (2.16±0.07; p=0.15) and of ePAH (2.15±0.10; p=0.14). Conclusions: Fractal dimension allows for non-invasive characterization of pulmonary vascular complexity. Using this method, patients with PAH or ePAH were found to have lower total and venous vascular complexities than controls without PAH or ePAH.

Varying perivascular astroglial endfoot dimensions along the vascular tree maintain perivascular-interstitial flux through the cortical mantle

The glymphatic system is a recently defined brain-wide network of perivascular spaces along which cerebrospinal fluid (CSF) and interstitial solutes exchange. Astrocyte endfeet encircling the perivascular space form a physical barrier in between these two compartments, and fluid and solutes that are not taken up by astrocytes move out of the perivascular space through the junctions in between astrocyte endfeet. However, little is known about the anatomical structure and the physiological roles of the astrocyte endfeet in regulating the local perivascular exchange. Here, visualizing astrocyte endfoot-endfoot junctions with immunofluorescent labeling against the protein megalencephalic leukoencephalopathy with subcortical cysts-1 (MLC1), we characterized endfoot dimensions along the mouse cerebrovascular tree. We observed marked heterogeneity in endfoot dimensions along vessels of different sizes, and of different types. Specifically, endfoot size was positively correlated with the vessel diameters, with large vessel segments surrounded by large endfeet and small vessel segments surrounded by small endfeet. This association was most pronounced along arterial, rather than venous segments. Computational modeling simulating vascular trees with uniform or varying endfeet dimensions demonstrates that varying endfoot dimensions maintain near constant perivascular-interstitial flux despite correspondingly declining perivascular pressures along the cerebrovascular tree through the cortical depth. These results describe a novel anatomical feature of perivascular astroglial endfeet and suggest that endfoot heterogeneity may be an evolutionary adaptation to maintain perivascular CSF-interstitial fluid exchange through deep brain structures.

The fractal geometry of bronchial trees differs by strain in mice

Fractal biological structures are pervasive throughout the plant and animal kingdoms, with the mammalian lung being a quintessential example. The lung airway and vascular trees are generated during embryogenesis from a small set of building codes similar to Turing mechanisms that create robust trees ideally suited to their functions. Whereas the blood flow pattern generated by these fractal trees has been shown to be genetically determined, the geometry of the trees has not. We explored a newly established repository providing high-resolution bronchial trees from the four most commonly studied laboratory mice (B6C3F1, BALB/c, C57BL/6 and CD-1). The data fit a fractal model well for all animals with the fractal dimensions ranging from 1.54 to 1.67, indicating that the conducting airway of mice can be considered a self-similar and space-filling structure. We determined that the fractal dimensions of these airway trees differed by strain but not sex, reinforcing the concept that airway branching patterns are encoded within the DNA. The observations also highlight that future study design and interpretations may need to consider differences in airway geometry between mouse strains. NEW & NOTEWORTHY Similar to larger mammals such as humans, the geometries of the bronchial tree in mice are fractal structures that have repeating patterns from the trachea to the terminal branches. The airway geometries of the four most commonly studied mice are different and need to be considered when comparing results that employ different mouse strains. This variability in mouse airway geometries should be incorporated into computer models exploring toxicology and aerosol deposition in mouse models.

Hemodynamics in the retinal vasculature during the progression of diabetic retinopathy

Purpose: In this study, it is shown that hemodynamic features are applicable as biomarkers to evaluate the progression of diabetic retinopathy (DR). Methods: Ninety-six fundus images from twenty-four subjects were selected. For each patient, four photographs were captured during the three years before DR and in the first year of DR. The vascular trees, which consisted of a parent vessel and two child branches were extracted, and at the branching nodes, the fluid dynamic conditions were estimated. Results: Veins were mostly affected during the last stage of diabetes before DR. In the arteries, the blood flow in both child branches and the Reynolds number in the smaller child branch were mostly affected. Conclusion: This study showed that hemodynamic features can add further information to the study of the progression of DR.